[unreadable] Benign breast disease (BBD) is emerging as an important diagnostic and therapeutic challenge. The increasingly widespread use of screening mammography has made it possible to detect early breast lesions clinically. Epidemiologic studies have provided evidence for a significant relationship between benign breast lesions and subsequent risk for breast cancer. And the results of prospective randomized chemoprevention trials have provided new pharmacologic options for breast cancer prevention to women at increased risk. The challenges to clinicians and their patients stem from the heterogeneous nature of benign breast disease and the lack of reliable criteria to accurately assign prognostic significance and determine clinical management for a biopsy finding. It appears that the limits of morphologic and histopathologic discrimination have been reached. Newer, molecular-based assays are needed to define risk categories with more rigor and accuracy. The Family Risk Assessment Program (FRAP) was established at the Fox Chase Cancer Center (FCCC) in 1991 by Dr. Mary Daly to assemble a cohort of families at increased risk for breast cancer based on family history of disease and/or personal history of benign breast disease for research purposes. To date, 784 women with a personal history of biopsy-proven benign breast disease are participating in FRAP. Dr. Godwin, a long time collaborator with Dr. Daly, has begun a series of experiments combining laser capture microdissection (LCM) and proteomic approaches to identify marker proteins in breast tissues. This collaboration provides an ideal opportunity to pilot the use of proteomics to identify novel markers of breast cancer risk in this population. The primary aims of this project are to explore the application of LCM and proteomic analyses to breast specimens with BBD and to validate those proteins found to be overexpressed using immunohistochemical approaches with BBD specimens from FRAP participants. A secondary aim is to correlate proteomic markers with traditional histopathologic definitions and to explore their correlation with other clinical and epidemiologic markers of risk. If promising, this work would lead to a larger prospective clinical research project to validate the findings of the pilot study and explore mechanisms of action. [unreadable] [unreadable]